PROJECT SUMMARY While the existence of multiple memory systems in the brain is generally accepted, it is not known how these different systems interact to result in continuously adaptive memory-guided behaviors and decisions. Recent results clearly show that particular combinations of memory-related brain systems show synchronized neural activity (at the population level, for example at the theta frequency) in a task-dependent way. Yet the informational and behavioral significance of such co-modulation of neural activity in not known perhaps in part because such measures are not temporally or informationally refine enough to reveal the significance of this interaction. This proposal aims to develop a novel paradigm for determining whether a specific type of information in one brain area can provide a signal to a connected memory structure to engage or disengage in its well-known memory-related function. Specifically, Aim 1 will test the causal relationship between neural signatures of planned behaviors in hippocampus and the regulation of working memory/action selection by the medial prefrontal cortex. Also, the subsequent impact of this neural directive on future action selection, as well as on future hippocampal place field integrity, will be examined. It is postulated that prefrontal cortex normally stabilizes place fields which in turn should enable rats to more quickly adapt to changing task conditions. Disruption of such prefrontal function, especially during the operation of working memory, should destabilize place fields and EEG phenomena that rely on fully function place fields. In addition, impaired choice accuracy is predicted. Aim 2 proposes to build on the exciting idea that hippocampal theta oscillates between periods of memory encoding and memory retrieval. The same open loop system that was developed in Aim 1 will be used to disrupt selectively working memory encoding or retrieval functions of the medial prefrontal cortex when encoding or retrieval are detected in hippocampus. The general prediction is that disrupting encoding in the prefrontal cortex will disproportionately impair the initial learning behavioral and neural processes relative to behavioral and neural processes that go on after learning has taken place. The combined results will provide new insight into the informational nature of communication between hippocampus and the prefrontal cortex. Also the closed loop paradigm can serve as an innovative and new model for studying the functional interactions between other memory and behavioral systems of the brain, which in turn can have tremendous clinical and therapeutic benefits. It may be possible to interfere with (in cases of unwanted specific associations) or facilitate (in cases of deficient desired associations) specific types of learning or learned associations that characterize a number of mental disorders.